For many chronically diseased areas, oral administration is generally considered as a desirable route of pharmaceutical administration in view of convenience and cost. However, many candidate compounds for medicinal products exhibit low absorbability when administered orally since they have a low membrane permeability in the gastrointestinal tract or they are unstable therein, thereby facing a condition of being unable to maintain the blood concentration for sufficient pharmacological effects.
Moreover, it is known that there are some organic compounds that show a tendency of being barely absorbed although they are reported to be recognized by influx transporters expressed in small-intestinal epithelial cells (for example, Sakamato et al., J. Antibiot. 38 (1985): 496-504, and Kelly et al., Clin. Pharmacokinet. 19 (1990): 177-196, etc.).
Given this circumstance, research has been conducted in using various absorption enhancers and enzyme inhibitors to improve the absorption of compounds that are candidates for medical products. For example, Swenson et al., (Adv. Drug Del. Rev. 8 (1992): 39-92) and Kompella et al., (Adv. Drug Del. Rev. 46 (2001): 211-245) disclose methods for using absorption enhancers to improve peptide absorption. However, these methods pose the problem of cell damage by the absorption enhancers, which are primarily added to enhance absorption.
Hayakawa et al., (Pharm. Res. 9 (1992): 535-540) and Zhou et al., (J. Control Rel. 29 (1994): 239-252) teach methods for adding enzyme inhibitors to inhibit decomposition and promote absorption in the gastrointestinal tract. However, these methods cause problems such that no substrate specificity is obtained in absorption.
Furthermore, to improve absorption of furosemide, which is recognized by an efflux transporter in the gastrointestinal tract, addition of a pH-sensitive polymer is known (e.g., Terao et al. J. Pharm. Pharmacol. 53 (2000): 433-440). However, this reference does not suggest the use of transporters to improve gastrointestinal absorption, and has, as with the prior art methods described above, the problem of not imparting substrate specificity to gastrointestinal absorption.
In addition, there have been no prior art methods that enhance the absorption of organic compounds that are, despite being substrates for influx transporters, of poor absorbability.